His first four years were spent in Huron country with the Jesuits where he learned Indian languages. By 1645 he was posted to the Trois-Rivières garrison as an interpreter, a clerk, and a soldier. In 1646 he moved to Fort Ville-Marie (at present-day Montreal) where he spent the remainder of his career and his life. On 28 May 1654 he married Catherine Primot and thereby establishing himself in a family associated with the fur business.

Le Moyne's career was highlighted by various Indian skirmishes, the most noteworthy of which may have been an ill-fated expedition to Iroquois country in 1666, ordered by Daniel de Rémy de Courcelle.

During his career, he received awards and honors involving money and land grants. He had two seigneurial titles conferred on him along with additional lands; in 1672 Governor Louis de Buade de Frontenac and Intendant of New France, Jean Talon confirmed the seigneury title of Longueuil. The following year Frontenac granted him a seigneury at Châteauguay. His eldest son, Charles, was given the Longueuil fief in 1684.